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MMR Vaccine
Measles Infection Measles is caused by a paramyxovirus that infects the respiratory system. Symptoms of this infection include a fever, cough, and general rash all over the body. The infection is spread by coming into contact with fluids of the nose and mouth of the infected individual. [1] Vaccine Development In the mid 1950s and early 1960s, researchers were making an effort to develop a vaccine for measles soon after the successful poliovirus vaccine was launched. The poliovirus vaccine was developed by John Enders and researchers at Harvard. These researchers were subsequently able to culture the measles virus in 1954. The original sample of measles virus was taken from a boy named David Edmonston. Shortly thereafter, Enders, Katz, and Holloway were able to attenuate the stain and introduce it into children, causing the production of measles antibodies (Hendriks et al., 2013). However, the first attenuated version was too reactive, and researchers had to work on reducing the stain’s reactivity. In order to accomplish this task, Enders made the Edmonston strain available to the research community. By 1963, two measles vaccines were introduced by pharmaceutical companies. Merck developed a live-virus vaccine, known as Rubeovax. Pfizer produced a formalin-inactivated (killed) version called Pfizer-vax Measles-K. Later that year, a survey was published after studying the dosage effects of both vaccines. The live version of the vaccine had been administered to 25,000 people, and although there were some side effects of fever and rash, antibody levels in patients were high. The attenuated version released by Pfizer did not seem to produce side effects, but antibody levels were much lower in patients. Due to these studies, it seemed like more protection against measles was offered by Merck’s live virus vaccine. However, due to the reaction side effects, more research was employed to make a less reactive live-virus vaccine. In 1968, Merck unveiled a more attenuated “Moraten” strain (Hendriks et al., 2013). Mumps Infection The agent of this viral disease is the mumps virus. Swelling of the salivary glands is common, particularly the parotid gland. The viral disease is spread through contact with saliva and respiratory secretions. [2] Vaccine Development The mumps paramyxovirus was successfully isolated in culture in 1945. The first vaccine to be developed was an inactivated version in 1948. However, this vaccine did not produce immune protection for very long and the vaccine was pulled off the market in the mid 1970’s. A live attenuated strain of mumps (from the Jeryl Lynn strain) vaccine was available in 1967, which later became a part of the MMR vaccine. The mumps vaccine is made in a fibroblast chick embryo culture (CDC Mumps Vaccine). Rubella Infection Rubella, derived from the Latin translation little red, is also called German measles. This disease manifests from the infection of rubella virus. The disease can either be “acquired” through the respiratory system, or congenitally through pregnancy. Symptoms of congenital rubella syndrome can be much more severe and life-threatening. Rubella can cause a rash on the face and body, as well as swelling of the lymph nodes and salivary glands. Congenital rubella syndrome can have severe effects on a newborn’s vision, heart, brain, and hearing.[3] Vaccine Development First described as congenital rubella syndrome (CRS), the primary case was recognized in 1941. Norman Gregg, an ophthalmologist, was the first to connect interuterine rubella with the development of congenital cataracts. Other symptoms were soon found to be associated with congenital rubella syndrome, including deafness and congenital heart disease (Plotkin 2006). As time progressed and more was unraveled, other symptoms and organs were found to be associated with the syndrome. After WWII, resources allowed for the study of rubella in the early 1960s. Not too long after, the rubella strain was successfully cultured. The isolation of the virus came at a key point in history, as there was a rubella epidemic from the years of 1963 to 1965. The isolation of the rubella virus was important for diagnosing individuals. However, there was no vaccine at the time of the rubella epidemic, highlighting the need to attenuate the virus. Extensive research ultimately was able to attenuate the virus, and between the years of 1969 and 1970 several live attenuated vaccines were released (Plotkin 2006). One particular live attenuated vaccine, RA 27/3, has historical significance. This human diploid cell line derived vaccine was first released to the public in Europe, but not the United States. Since the vaccine was derived from a human cell line, many believed that it contained human contaminants. The next decade proved quite the contrary; the RA 27/3 vaccine was doing well in Europe. Furthermore, some of the animal-derived vaccines were having issues with rubella infection even after vaccination. This was not the case with the RA 27/3 vaccine in Europe. Due to this evidence, many fought for the licensing of the RA 27/3 vaccine in the United States, including Maurice Hilleman at Merck. Hilleman was looking for the right components to develop the combined measles, mumps, and rubella vaccine. Measles, Mumps, and Rubella Combined Vaccine (M-M-R II) Originally licensed as M-M-RTM in 1971, a new version was released in 1971: M-M-RTM II. This version had a replacement of the rubella strain from HPV-77 DE with RA 27/3 (Lievano et al., 2012). Since 1987, the same vaccine has been used. Owned by Merck, Sharp, and Dohome Corp, and is given to individuals 12 months and older. All three viruses are live attenuated versions of the MMR vaccine. Attenuation is important for making the virus less virulent, but still strong enough for sufficient antibody generation. Antibody levels are much lower in killed-virus versions of vaccines (which does not include the MMR vaccine). The process of attenuation involves introduction and passage in a host, such as a live animal, cells in tissue culture, or egg embryos [4{]. When grown in tissue culture conditions, researchers are able to select less virulent versions of the virus, or ones which have a mutation in genes required for virulence. References Hendriks J and Blume S. Measles Vaccination Before the Measles-Mumps Rubella Vaccine. American Journal of Public Health 2013 (8): 1393-1401. Lievano F, Galea SA, Thornton M, Wiedmann RT, Manoff SB, Tran TN, Amin MA, Seminack MM, Vagie KA, Dana A, Plotkin SA. Measles, mumps, and rubella virus vaccine (M-M-R II): A review of 32 of clinical and postmarketing experience. Vaccine 2012 (30): 6918-6926. Plotkin SA. The History of Rubella and Rubella Vaccination Leading to Elimination. CID 2006: 43. Centers for Disease Control and Prevention: Mumps Vaccine Measles Wiki Mumps Wiki Rubella Wiki Attenuated Vaccine